Routine coronary angiography provides anatomical information which only partially predicts prognosis and response to therapy. These images also contain information about the distribution of coronary blood flow which is less conspicuous. Digital coronary angiography can enhance visualization of contrast material in the myocardial microcirculation and permit quantification of regional time contrast density function. Nevertheless, reliable measurement of myocardial perfusion has not been achieved due in part to: 1. inaccurate densitometry, and 2. inadequate quantitation algorithms. The long range purpose of this grant is to reduce these sources of error by apply linear systems theory for quantification of regional myocardial perfusion and coronary vasodilator reserve. The specific aims are: 1. develop linear analytical algorithms to describe contrast transit through the coronary circulation, 2. evaluate and develop digital angiography as a linear processing system for densitometry, 3. determine if, and over what range of conditions, the coronary circulation behaves as a linear system, thereby permitting application of linear analysis, 4. establish the accuracy and reproducibility of these methods by correlation with independent measurements of regional myocardial perfusion and by measurements during states of altered coronary physiology, and 5. develop these methods for routine clinical use. To achieve these aims digital coronary angiography will be used to acquire time-density functions at the sites of contrast injection and distribution in the microcirculation, thus defining a regional coronary circulatory system. The system transfer function will be computed by iterative convolution of these data with a lagged-normal density mathematical model of contrast transit. The mean transit time of the transfer function will serve as a composite index of flow and coronary reserve. Dynamic x-ray phantom models will be used for algorithm testing and analysis of densitometric errors. These methods will be validated in animal studies using electromagnetic flow measurement and radiolabeled microspheres to quantitate regional myocardial perfusion and Doppler velocity probes to assess coronary reserve. The potential health-related benefits of this research are improved diagnostic and clinical decision making capability of coronary angiography with minimal additional risk by quantitative assessment of the functional significance of atherosclerotic coronary artery disease.